Abstract
Hematopoietic cell transplantation (HCT) is often a last resort, but potentially curative treatment option for children suffering from hematological malignancies and a variety of non-malignant disorders, such as bone marrow failure, inborn metabolic disease or immune deficiencies. Although efficacy and safety of the HCT procedure has increased significantly over the last decades, the majority of the patients still suffer from severe acute toxicity, viral reactivation, acute or chronic graft-versus-host disease (GvHD) and/or, in case of malignant disease, relapses. Factors influencing HCT outcomes are numerous and versatile. For example, there is variation in the selected graft sources, type of infused cell subsets, cell doses, and the protocols used for conditioning, as well as immune suppression and treatment of adverse events. Moreover, recent pharmacokinetic studies show that medications used in the conditioning regimen (e.g., busulphan, fludarabine, anti-thymocyte globulin) should be dosed patient-specific to achieve optimal exposure in every individual patient. Due to this multitude of variables and site-specific policies/preferences, harmonization between HCT centers is still difficult to achieve. Literature shows that adequate immune recovery post-HCT limits both relapse and non-relapse mortality (death due to viral reactivations and GvHD). Monitoring immune parameters post-HCT may facilitate a timely prediction of outcome. The use of standardized assays to measure immune parameters would facilitate a fast comparison between different strategies tested in different centers or between different clinical trials. We here discuss immune cell markers that may contribute to clinical decision making and may be worth to standardize in multicenter collaborations for future trials.
Highlights
The probability of long-term survival after hematopoietic cell transplantation (HCT) has steadily improved in the last decade with advances in treatments [1, 2]
Transplantation with matched related bone marrow (BM) or peripheral blood (PB) cells is considered the standard for allo-HCT, and matched unrelated donors (MUD)matched unrelated cord blood (CB), a haplo-identical or a mismatched family donor can be considered as alternative graft sources
The HCT-source and its manipulation, such as CD34+ positive selection [13] or other ex vivo T-cell depletion [14] and in vivo T cell depletion with serotherapy [e.g., anti-thymocyte globulin (ATG) or Alemtuzumab] may be important factors defining the probability of T-cell immune reconstitution (IR)
Summary
The probability of long-term survival after hematopoietic cell transplantation (HCT) has steadily improved in the last decade with advances in treatments [1, 2]. This study nicely illustrates that it is essential to understand the effects of all agents on immune reconstitution and the interrelationships between the agents that may significantly alter the outcomes In this trial, patients receiving total body irradiation (TBI) + cyclophosphamide (Cy) had lower “absolute lymphocyte counts” on the day of rATLG dosing compared to patients receiving a chemo (Bu-Cy or Bu-Flu)-based regimen or patients that received Cy first, before receiving TBI (usually because of practical issues). Patients with adequate CD4 T cell numbers should be monitored carefully, but would not receive treatment, as there is a reasonable chance that the reconstituting immune system will clear the pathogen by itself These observations should be further studied in the context of a clinical trial, and follow-up studies and validations are needed to confirm whether predictions can be further improved. As different institutions have their own policies on sample collection and monitoring, it is of crucial importance to set up multicenter validation trials to establish standardized protocols for sampling, handling logistics, measurements and data processing, to reduce result variability and allow for more accurate data comparison
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